This invention relates generally to measuring analytes in biological fluids, such as whole blood samples, using optical instruments. Such instruments normally will be tested using solutions that mimic the usual biological sample and contain a known amount of the analyte. The present invention is concerned with identifying a sample as a test solution, commonly called a control solution. More particularly, the invention relates to preventing optical instruments from including in their retained history of measurements those made of the analyte in control solutions. That is, avoiding errors that may occur when the retained history does not accurately report the content of samples previously measured, but includes the results obtained with control solutions.
The quantitative determination of analytes in biological fluids is of great importance in diagnosing and treating medical problems, such as measuring the glucose level in biological fluids, which is important to diabetic individuals. The present invention will be described as it is applied to measuring glucose in blood samples. However, the invention may be applied to other analytes measured in optical instruments.
Both electrochemical and optical methods are used to measure the glucose content of blood. This invention relates to optical measurements. Color changes developed by chemical reactions with the glucose in blood can be measured optically by several types of instruments, including diffuse reflectance, transmittance, absorbance, diffuse transmittance, total transmittance and the like. For example, diffuse reflectance is used in the methods described in U.S. Pat. Nos. 5,611,999 and 6,181,417. Light from light emitting diodes (LEDs) is directed onto a substrate that has been in contact with blood and has developed an optically measurable response. Reflected light is directed to a photodetector where the amount of light received is measured, and correlated with the amount of glucose in the blood sample. In the examples below the absorbance of light was used.
Several types of chemical reactions have been used to cause a change that is detectable by optical instruments. These include reacting glucose with glucose oxidase or glucose dehydrogenase to develop colors which indicate the quantity of glucose in the sample being tested. See for example U.S. Pat. No. 4,689,309. The present invention is not considered to be limited by the type of the chemical reaction used to determine the amount of glucose in blood, provided only that the response to glucose in the sample is detectable by optical instruments.
In order for accurate measurements to be assured, control solutions containing known amounts of glucose are used to verify that the instrument is operating properly. The composition of control solutions has been the subject of a number of patents and publications. Representative are U.S. Pat. Nos. 3,920,580; 4,572,899; 4,729,959; 5,028,542; and 5,605,837; WO 93/21928; WO 95/13535; and WO 95/13536. While control solutions containing blood serum have been used, the more recent patents have been concerned with replacing serum-based control solutions with solutions free of serum, since serum-free solutions are more consistent and stable than those containing serum. The control solution should behave in a manner similar to blood if glucose is to be accurately measured. It will be evident that the composition must be stable over lengthy periods of storage before use. Further, the composition must allow the glucose to react with the reagents that produce color in a manner corresponding to that of glucose contained in a blood sample. Also, the composition should not respond to the light used to illuminate a sample in a way that interferes with the reading of the color developed by reaction of the glucose content with the reagents. Thus, improving the composition of control solutions has been of considerable interest in the art.
Although some control solutions do not add color, others do include colored additives to provide the appearance of blood. For example, U.S. Pat. No. 3,920,580 suggests adding red dye and U.S. Pat. No. 5,605,837 includes a suspension of black particles.
A problem arising in certain instruments relates to the need to distinguish between measurements made with blood samples and those made with control solutions, which are frequently used to assure that the test equipment is performing correctly. If the control solution is formulated to respond in a manner similar to that of a whole blood sample, the instrument does not recognize that a control solution is being tested rather than a blood sample. That is, the glucose content is determined independently of the rest of the sample so that the control solution provides an accurate reading. However, it is common for such instruments to record the glucose measurement and store it, since the history of glucose measurements can be very useful in treating a diabetic patient. Obviously, the glucose content of control solutions should not be included in the recorded history, unless that data can be identified and separated from the glucose measurements of blood samples. Of course, that could be done manually by the user, but through inadvertence the glucose history could be distorted. It would be preferable that the user not be responsible for separating the glucose measurement made of control solutions and blood sample.
In U.S. Pat. No. 5,723,284 electrochemical measurement of glucose in blood is discussed. The '284 patent proposed to modify the control solutions so that the meter would recognize that a control solution was being measured and take appropriate action to prevent the results from being included in the blood sample results. The present invention includes a means for recognizing the presence of a control solution in instruments that measure glucose or other analytes by optical means, as will be described in detail below.